---
title: "GLP-1 receptor agonists and reports of depressed mood and suicidal thoughts in type 2 diabetes"
id: "pubmed-42002107"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42002107"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42002107/"
doi: "10.1016/j.jad.2026.121802"
published_at: "2026-08-15T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# GLP-1 receptor agonists and reports of depressed mood and suicidal thoughts in type 2 diabetes
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42002107
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42002107/)
- **DOI:** [10.1016/j.jad.2026.121802](https://doi.org/10.1016%2Fj.jad.2026.121802)
- **Published At:** 2026-08-15T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This VigiBase disproportionality study examined reports of **depressed mood** and **suicidal thoughts** associated with glucagon-like peptide-1 receptor agonists (**GLP-1RAs**) in patients with type 2 diabetes mellitus (T2DM) from 2010–2024. - Investigators identified 1,183,817 adverse events related to GLP-1RAs in the WHO database. - Signals for increased reporting of depressed mood were observed with **semaglutide**, **liraglutide**, and **tirzepatide** (adjusted ROR0.25: 2.13, 1.52, 1.07, respectively). - Signals for increased reporting of suicidal thoughts were also seen for the same agents (adjusted ROR0.25: 6.76, 2.43, 3.39, respectively). - No disproportionality signal was detected for suicide attempts or completed suicide. Absolute reporting frequencies of mood and suicidality events were low. - Concomitant **antidepressant** use among reports was 2.3–5 times more frequent for GLP-1RAs compared with other glucose-lowering medications. - Documented comorbid depression was 25%–120% higher in GLP-1RA reports than in comparators. - Median time-to-onset for reported depressed mood or suicidal thoughts was 96 days; survival analysis showed an early rise in reporting followed by stabilization. - Adjustment for antidepressant use modestly reduced the associations. - Authors applied the Bradford Hill criteria and concluded findings are compatible with a model where underlying affective vulnerability or reporting factors drive the associations rather than a uniform drug-specific effect. - Clinical implication: GLP-1RAs remain clinically valuable for T2DM, but psychiatric monitoring during early treatment in vulnerable patients is advised.
## Clinical Analysis & Structured Key Points
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Epub 2026 Apr 17. # Depressed mood and suicidal thoughts reporting with GLP-1 receptor agonists in type 2 diabetes: A WHO VigiBase study [Mohammed Aboukaoud](https://pubmed.ncbi.nlm.nih.gov/?term=Aboukaoud+M&cauthor_id=42002107)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42002107/#full-view-affiliation-1 "Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel. Electronic address: mohammed.aboukaoud@sheba.health.gov.il."), [Bosmat Hoch](https://pubmed.ncbi.nlm.nih.gov/?term=Hoch+B&cauthor_id=42002107)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42002107/#full-view-affiliation-2 "Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel."), [Mark Weiser](https://pubmed.ncbi.nlm.nih.gov/?term=Weiser+M&cauthor_id=42002107)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42002107/#full-view-affiliation-3 "Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel; Gray Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel."), [Revital Amiaz](https://pubmed.ncbi.nlm.nih.gov/?term=Amiaz+R&cauthor_id=42002107)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42002107/#full-view-affiliation-3 "Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel; Gray Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.") Affiliations Expand ### Affiliations * 1 Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel. Electronic address: mohammed.aboukaoud@sheba.health.gov.il. * 2 Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel. * 3 Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel; Gray Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel. * PMID: **42002107** * DOI: [ 10.1016/j.jad.2026.121802 ](https://doi.org/10.1016/j.jad.2026.121802) Free article Item in Clipboard # Depressed mood and suicidal thoughts reporting with GLP-1 receptor agonists in type 2 diabetes: A WHO VigiBase study Mohammed Aboukaoud et al. J Affect Disord. 2026. Free article Show details Display options Display options Format Abstract PubMed PMID J Affect Disord Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22J+Affect+Disord%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22J+Affect+Disord%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42002107/) . 2026 Aug 15:407:121802. doi: 10.1016/j.jad.2026.121802. Epub 2026 Apr 17. ### Authors [Mohammed Aboukaoud](https://pubmed.ncbi.nlm.nih.gov/?term=Aboukaoud+M&cauthor_id=42002107)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42002107/#short-view-affiliation-1 "Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel. Electronic address: mohammed.aboukaoud@sheba.health.gov.il."), [Bosmat Hoch](https://pubmed.ncbi.nlm.nih.gov/?term=Hoch+B&cauthor_id=42002107)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42002107/#short-view-affiliation-2 "Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel."), [Mark Weiser](https://pubmed.ncbi.nlm.nih.gov/?term=Weiser+M&cauthor_id=42002107)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42002107/#short-view-affiliation-3 "Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel; Gray Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel."), [Revital Amiaz](https://pubmed.ncbi.nlm.nih.gov/?term=Amiaz+R&cauthor_id=42002107)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42002107/#short-view-affiliation-3 "Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel; Gray Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.") ### Affiliations * 1 Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel. Electronic address: mohammed.aboukaoud@sheba.health.gov.il. * 2 Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel. * 3 Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel; Gray Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel. * PMID: **42002107** * DOI: [ 10.1016/j.jad.2026.121802 ](https://doi.org/10.1016/j.jad.2026.121802) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Introduction:** Evidence regarding depression and suicidality with glucagon-like peptide-1 receptor agonists (GLP-1RAs) remains inconsistent, particularly in patients with type 2 diabetes mellitus (T2DM) and underlying affective vulnerability. **Methods:** We conducted a disproportionality analysis of the WHO VigiBase (2010-2024), including T2DM patients. Reports of depressed mood and suicidal thoughts associated with GLP-1RAs were compared with other glucose-lowering medications. Analyses incorporated age, sex, time-to-onset, dose, comorbid depression, and concomitant antidepressant use. Adjusted reporting odds ratios (RORs) and a Weibull time-to-event model were applied. Causality was explored using Bradford Hill criteria. **Results:** A total of 1,183,817 adverse events related to GLP-1RA were identified. Depressed mood and suicidality signals were observed with semaglutide, liraglutide, and tirzepatide (adjusted ROR0.25: 2.13, 1.52, 1.07) and (adjusted ROR0.25: 6.76, 2.43, 3.39), respectively. No signal was identified for suicide attempts or completed suicide. Absolute reporting frequencies were low. Concomitant antidepressant use was 2.3-5 times more frequent, and comorbid depression 25%-120% higher, compared with other glucose-lowering medications. Median time-to-onset was 96 days. Survival analysis demonstrated an early increase in reporting followed by stabilization over time. Adjustment for antidepressant use modestly attenuated associations. **Conclusion:** GLP-1RAs were associated with increased reporting of depressed mood and suicidal thoughts, particularly in patients receiving concomitant antidepressants. These findings support a patient-centered model in which underlying affective vulnerability or reporting factors drive reported mood symptoms rather than a uniform drug-specific effect. GLP-1RAs remain clinically valuable, but psychiatric monitoring during early treatment in vulnerable patients is warranted. **Keywords:** Completed suicide; Depressed mood; Depression; GLP-1RA; Suicidal attempt; Suicidal thoughts. Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of competing interest The authors, Mohammed Aboukaoud, Bosmat Hoch, Mark Weiser, and Revital Amiaz, have no conflicts of interest to declare and no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ## Similar articles * [ The association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicidality: reports to the Food and Drug Administration Adverse Event Reporting System (FAERS). ](https://pubmed.ncbi.nlm.nih.gov/38087976/) McIntyre RS, Mansur RB, Rosenblat JD, Kwan ATH.McIntyre RS, et al.Expert Opin Drug Saf. 2024 Jan;23(1):47-55. doi: 10.1080/14740338.2023.2295397. Epub 2023 Dec 19.Expert Opin Drug Saf. 2024.PMID: 38087976 * [ Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicidality: A replication study using reports to the World Health Organization pharmacovigilance database (VigiBase®). ](https://pubmed.ncbi.nlm.nih.gov/39433133/) McIntyre RS, Mansur RB, Rosenblat JD, Rhee TG, Cao B, Teopiz KM, Wong S, Le GH, Ho R, Kwan ATH.McIntyre RS, et al.J Affect Disord. 2025 Jan 15;369:922-927. doi: 10.1016/j.jad.2024.10.062. Epub 2024 Oct 19.J Affect Disord. 2025.PMID: 39433133 * [ Comparative pharmacovigilance analysis of suicidality-related adverse events among GLP-1 and non-GLP-1 anti-obesity drugs in the FDA Adverse Event Reporting System. ](https://pubmed.ncbi.nlm.nih.gov/41739406/) Seijas-Amigo J, Salgado-Barreira Á, Rodriguez-Penas D, Cardeso-Paredes B, Ribeiro-Ferreiro M, Rodriguez-Mañero M, Gonzalez-Juanatey JR.Seijas-Amigo J, et al.Int J Clin Pharm. 2026 Jun;48(3):1026-1035. doi: 10.1007/s11096-026-02099-y. Epub 2026 Feb 25.Int J Clin Pharm. 2026.PMID: 41739406Free PMC article. * [ Real-world evidence on the utilization, clinical and comparative effectiveness, and adverse effects of newer GLP-1RA-based weight-loss therapies. ](https://pubmed.ncbi.nlm.nih.gov/40196933/) Thomsen RW, Mailhac A, Løhde JB, Pottegård A.Thomsen RW, et al.Diabetes Obes Metab. 2025 Apr;27 Suppl 2(Suppl 2):66-88. doi: 10.1111/dom.16364. Epub 2025 Apr 8.Diabetes Obes Metab. 2025.PMID: 40196933Free PMC article.Review. * [ Assessing the shadows: A meta-analysis of GLP-1 agonists and suicidal ideation. ](https://pubmed.ncbi.nlm.nih.gov/41366934/) Alansari AO, Alharbi AS, Alshehri KM, Alhabib AT, Alsalmi BS, Almosfer WA, AlAjlan FA, Alharbi AA, Alzahrani BS, Alamer B, Alatawi AM.Alansari AO, et al.Medicine (Baltimore). 2025 Dec 5;104(49):e46173. doi: 10.1097/MD.0000000000046173.Medicine (Baltimore). 2025.PMID: 41366934Free PMC article. 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